Autonomic function such as arterial pressure (AP), heart rate (HR), and respiration is quite stable and show the constant value during non-rapid eye movement (non-REM) sleep, but significantly fluctuates during REM sleep. However, the central mechanism for AP and HR changes associated with REM sleep remains unclear. Adenosine is an endogenous sleep substance. Dopamine serves as an AP regulator. An antagonistic interaction between adenosine A_<2A> receptor (A_<2A>R) and dopamine D_2 receptor has been well known. In this study, we simultaneously recorded electroencepharogram (EEG), electromyogram (EMG), AP, and HR in wild-type and the A_<2A>R gene-knockout (KO) mice to clarify the role of A_<2A>R in REM sleep-related cardiovascular function.An A_<2A>R agonist (CGS-21680) induced sleep as judged by EEG and EMG recordings. In vivo microdialysis revealed that this agonist inhibited histamine release in both the frontal cortex and medial pre-optic area in a dose-dependent manner, and increased GABA release specifically in the histaminergic tuberomammillary nucleus but not in the frontal cortex. These results suggest that the A_<2A>R agonist induced sleep by inhibiting the histaminergic arousal system through increasing GABA release.In wild-type mice, mean AP decreased during REM sleep, transiently dropped at REM sleep-offset, and then recovered to the basal level. HR also decreased during REM sleep, quickly increased at REM sleep-offset, and then recovered to the basal level. On the other hand, in A_<2A> KO mice, both mean AP and HR remarkably increased during REM sleep and then decreased quickly at REM sleep-offset. These results, taken together, indicate that A_<2A>R is involved in the autonomic regulation during REM sleep.